Behavioral or Solifenacin Therapy for Urinary Symptoms in Parkinson Disease

The number of persons with Parkinson Disease (PD) in the United States is expected to double
by 2030 as the population ages. Importantly, this increase in the prevalence of PD will have
greater impact within the Department of Veterans Affairs (VA) because the Veteran population
is older than the general population and Veterans with PD are more likely than those without
PD to rely solely on VA for their health care. While PD is often characterized by the motor
symptoms of the disease (tremor, bradykinesia, rigidity), non-motor symptoms such as urinary
symptoms correlate more closely with impaired well-being as the disease progresses. However,
the impact of urinary symptoms in PD extends beyond worsened well-being. The urinary symptoms
of overactive bladder (OAB), including urgency, frequency, and nocturia, with or without
urinary incontinence, are the most common urinary symptoms of PD. OAB symptoms are associated
with falls (a cause of increased mortality in PD), with spouse/caregiver stress, and,
ultimately with institutionalization, thus it is critical that we optimize the care of
urinary symptoms for Veterans with PD.

Several studies suggest abnormal central nervous system processing of sensory input from
bladder afferent nerves contributes to OAB symptoms in PD, possibly because of delayed
recognition of bladder fullness. This mirrors findings in non-PD populations with OAB. In the
non-PD OAB population, pelvic floor muscle contractions diminish bladder muscle contraction
and recent evidence demonstrates that behavioral training with pelvic floor muscle exercises
improves the cortical integration of bladder afferent signals. Pelvic floor muscle
exercise-based behavioral therapy for OAB symptoms requires individuals to learn a motor
skill and implement an adaptive behavioral strategy to delay the need to void. Because of its
effectiveness compared to drug therapy, pelvic floor muscle exercise-based behavioral therapy
is recommended first-line in men and women with OAB who do not have PD. However, the most
recent clinical guidelines for the treatment of urinary symptoms in PD recommend treatment
with anticholinergic drugs. While some anticholinergic drugs are effective in reducing
symptoms of OAB, it is important to note that there is a glaring lack of an empirical
evidence base to promote these drugs in the setting of PD given that they add to the
anticholinergic burden of antiparkinsonian therapy, and may worsen the cognitive and
autonomic burdens of the illness. Therefore, randomized controlled trials (RCTs) are needed
to optimize treatment paradigms for urinary symptoms in PD.

The investigators propose a three-site, RCT conducted at the Atlanta (lead site), Birmingham
and Richmond VA's to establish non-inferiority of pelvic floor muscle exercise-based
behavioral therapy compared to drug therapy for OAB symptoms in adults with PD. Groups will
be stratified by OAB symptom severity, PD motor symptom severity, gender, and site. The
investigators will randomize 90 participants in order to complete the study in 80
participants, assuming 85% power and a non-inferiority margin for the OAB symptom score of
15% at 12-weeks. The primary outcome measure will be urinary symptom severity as measured by
the International Consultation on Incontinence Questionnaire (ICIQ)-OAB symptom score
collected at 3 time points during the study: baseline, 6 weeks, and 12 weeks. The
investigators' benchmark for successful treatment will be a 2 point reduction in the ICIQ-OAB
symptom score, which corresponds with perceived benefit in preliminary studies of behavioral
therapy treatment for OAB symptoms in PD. To evaluate the primary efficacy outcome, the
investigators will utilize a random effects mixed model and adjust for baseline OAB symptom
score severity. Additionally, in order to better understand central control mechanisms of
bladder function, the investigators will determine if domain-specific cognitive function
impacts the response to exercise-based behavioral therapy or drug therapy for urinary
symptoms. At baseline and 12 weeks, randomized participants will undergo a brief
neuropsychological battery. Understanding how domain-specific cognitive function impacts
response to treatment may inform new targets for rehabilitation therapy.

Inclusion Criteria:

- Clinical diagnosis of PD determined by a board-certified neurologist with specialty
training in movement disorders

- An ICIQ-OAB Symptom Score of 7, which indicates clinically significant symptoms of
OAB, defined as presence of urinary urgency with or without urgency incontinence
usually with increased daytime frequency and nocturia in the absence of infection or
other obvious pathology

Exclusion Criteria:

- Significant cognitive impairment, as indicated by a Montreal Cognitive Assessment
(MoCA) score of < 18, which is the recommended diagnostic cutpoint for dementia in PD.

- Previous intensive pelvic floor muscle exercise training

- Clinically significant depression as measured by a Geriatric Depression Scale-Short
Form score 10 which could affect motivation to fully engage in the intervention

- Use of an indwelling urinary catheter

- Post-void residual (PVR) urine measurement by bladder ultrasound of 150 mL

- Severe uterine prolapse past the vaginal introitus

- Poorly controlled diabetes defined by a hemoglobin A1c (HgbA1c) of >9.0% within the
last 3 months. Participants with poorly controlled diabetes will be offered enrollment
if the OAB symptoms persist after improvement in diabetes control

- Chronic renal failure and on hemodialysis

- Genitourinary cancer with ongoing surgical or external beam radiation treatment

- Previous artificial urinary sphincter, sling procedure or implanted sacral
neuromodulation device

- History of bladder-injection of botulinum toxin in the last 12 months

- Any unstable health condition expected to result in hospitalization or death within in
the next 3 months as determined by site principal investigator.

- Hypersensitivity to drug class

- Contraindication to the study drug (solifenacin) including: narrow angle glaucoma,
history of gastric retention, history of acute urinary retention requiring
catheterization

- Current use of a bladder relaxant - permitted to enroll after two week washout

- Hematuria on microscopic examination in the absence of infection. A urologic
consultation will be recommended and enrollment will depend on clearance by a
urologist and agreement by the site PI that entry into the treatment protocol is not
contraindicated

- If on diuretic, dose should be stable for at least 4 weeks

- If taking an alpha-blocker, dose should be stable for at least 4 weeks

- If taking dutasteride or finasteride, dose should be stable for at least 6 months